We previously noted that melanomas developing in Cdk4^R24C/R24C::Tyr-NRAS, Arf^−/−::Tyr-NRAS and Trp53^F/F::Tyr-Cre(ER)::Tyr-NRAS mice exhibited differences in behaviour in vivo. We investigated this phenomenon using global gene expression profiling of lesions from the respective genotypes. While those from the Cdk4- and Arf-mutant mice exhibited similar profiles, the Trp53^F/F::Tyr-Cre(ER)::Tyr-NRAS melanomas were strikingly different, showing relative down-regulation of melanocyte-related genes, and up-regulation of genes related to neural differentiation. Specifically, they highly expressed genes representative of the myelin-producing peripheral oligodendrite (Schwann cell) lineage, although histopathologically the lesions did not exhibit the classical features of schwannoma. As Schwann cell precursors can be a cellular origin of melanocytes, it is unsurprising that plasticity with respect to melanocyte-neural differentiation can occur in melanoma. What is surprising is the genotype proclivity. Comparison of gene expression signatures revealed that melanomas from the Trp53-mutant mice show significant similarities with a subset of aggressive human melanomas with relatively low levels of MITF.

Item Type:	Refereed Article
Research Division:	Medical and Health Sciences
Research Group:	Oncology and Carcinogenesis
Research Field:	Cancer Cell Biology
Objective Division:	Health
Objective Group:	Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:	Skin and Related Disorders
Author:	Muller, HK (Professor Konrad Muller)
ID Code:	88737
Year Published:	2013
Web of Science® Times Cited:	7
Deposited By:	Medicine (Discipline)
Deposited On:	2014-02-13
Last Modified:	2014-05-15
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